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Brain and Central Nervous System TumorsPhase 1NCT00623077

MT2004-30: Tomotherapy for Solid Tumors

A Phase 1 study testing filgrastim, busulfan and etoposide in people with Brain and Central Nervous System Tumors and Kidney Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: A peripheral blood stem cell transplant or bone marrow transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy and image-guided intensity-modulated radiation therapy used to kill tumor cells. Read more about this study

Who is it for?
Ages Up to 70 years
What is being tested?
filgrastim, busulfan and etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
Aug 2005to Oct 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Diagnosis Patients must have had histologic verification of malignancy at original diagnosis. Diseases included are:
  • Ewing's Family Tumors (ES/PNET/DSRCT): metastatic at the time of diagnosis and/or relapsed after therapy
  • Renal tumors: relapsed (all histology-Wilm's tumor) or at diagnosis (clear cell sarcoma and Rhabdoid tumor),
  • Hepatoblastoma: metastatic at the time of diagnosis and/or relapsed after therapy
  • Rhabdomyosarcoma: metastatic at the time of diagnosis and/or relapsed after therapy
  • Soft tissue sarcomas: chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
Show all 18Show fewer
  • Primary Malignant Brain Neoplasms at diagnosis and/or relapse
  • Retinoblastoma: disseminated at diagnosis and/or relapsed
  • Other High Risk Metastatic or Relapsed Solid Tumors: To be approved by two or more physicians on the study committee
  • Disease Status: Patients must have either: 1) no evidence of disease or 2) stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or computated tomography (CT) and/or magnetic resonance imaging [MRI]) within 4 weeks of study entry.
  • Age: Patients must be 0-70 years of age at the time of study entry.
  • Performance Level: Karnofsky > or = 50% for patients > 10 years of age and Lansky > or = 50% for patients < or = 10 years of age. Note: Neurologic deficits in patients with central nervous system (CNS) tumors must be stable for a minimum of 1 week prior to study entry.
  • Organ Function:
  • Hematologic: prior to receiving total marrow irradiation (TMI) patients should have a hemoglobin of >10 gm/dl and a platelet count > 20,000/μl. Patients may receive transfusions as necessary.
  • Renal: glomerular flow rate (GFR) ≥ 50 ml/min/1.73m^2 or serum creatinine ≤ 2.5 x upper limit of normal (ULN) for age
  • Hepatic: aspartate aminotransferase/alanine aminotransferase (AST or ALT) ≤ 5 x ULN and bilirubin ≤ 5 x ULN
  • Cardiac: ejection fraction > 45% or no clinical evidence of heart failure
  • Pulmonary: oxygen saturation > 92% at rest (on room air)

Who cannot join

  • Disease Status: patients with progressive, non-therapy responsive disease will not be eligible.
  • Infection: patients who have active, uncontrolled infections or those who are HIV+.
  • Pregnancy or Breast-Feeding: pregnant or breast-feeding women will not be entered on this study.
  • Prior Radiation Therapy: patients must be eligible to receive TMI via tomographic radiation therapy (as determined by radiation oncology staff). If not eligible (due to extensive prior radiation or other circumstances), patients can be treated on study but will not receive radiation and will be analyzed on a separate arm.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Dose Escalation of Total Marrow Irradiation Added to an Alkylator-Intense Conditioning Regimen for Patients With High Risk or Relapsed Solid Tumors

RATIONALE: A peripheral blood stem cell transplant or bone marrow transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy and image-guided intensity-modulated radiation therapy used to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bone marrow radiation therapy followed by an autologous stem cell transplant in treating patients with high-risk or relapsed solid tumors.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose of tomographic total marrow irradiation (TMI) when given prior to an alkylator-intensive conditioning regimen in patients with high-risk or relapsed solid tumors.

Secondary

  • To determine the feasibility of performing positron emission tomography (PET) scans and spot radiation to PET-positive lesions after transplantation.
  • To determine the change in bone mineral density and turnover in patients treated with an alkylator-intensive conditioning regimen and TMI.

OUTLINE:

  • Mobilization chemotherapy and peripheral blood progenitor cell (PBPC) collection: Patients receive ifosfamide intravenously (IV) and etoposide IV on days -100 through -30.

Beginning 24 hours after completion of chemotherapy, patients receive filgrastim (G-CSF) subcutaneously (SC) or IV until blood counts recover. Patients then receive an increased dose of G-CSF SC or IV once daily for 3 consecutive days. Beginning on day -97, patients undergo up to 4 collections of PBPCs. Patients who do not yield an adequate number of cells undergo bone marrow harvest.

  • Bone marrow harvest: Patients undergo bone marrow aspirate and biopsy 2 weeks after the last dose of G-CSF. If the aspirate or biopsy is morphologically free of tumor cells and demonstrates > 20% cellularity, then patients receive sargramostim (GM-CSF) daily for 5 days followed by bone marrow harvest.
  • Total marrow irradiation (TMI) with tomotherapy: Patients undergo escalating doses of TMI* to all bony sites using helical tomotherapy image-guided intensity-modulated radiotherapy on days -11 to -9.

NOTE: *Patients with primary CNS tumors do not receive TMI but are eligible to receive chemotherapy and hematopoietic progenitor cell rescue in accordance with the protocol.

  • Conditioning regimen: Patients receive busulfan IV over 2 hours four times daily on days -8 to -6, high-dose melphalan IV over 30 minutes on days -5 to -4, and thiotepa IV over 2 hours on days -3 to -2.
  • Autologous CD34+ hematopoietic progenitor cell transplantation: Patients undergo reinfusion of autologous G-CSF-mobilized peripheral blood or bone marrow progenitor cells on day 0. Patients also receive G-CSF support beginning on day 0 and continuing until blood counts recover for 2 consecutive days.
  • Post-transplantation radiotherapy: Patients may receive additional radiotherapy to areas of known metastatic disease, PET-positive lesions, primary disease (if not previously irradiated to maximum tolerated dose), and lungs beginning on day 60 post transplantation. Patients with prior lung metastasis may receive up to 10 fractions of whole-lung irradiation.

Patients may also receive additional radiotherapy to primary disease if maximum tolerated dose has not yet been reached.

Patients undergo bone mineral density studies at baseline and at days 60, 120, and 180 post transplantation. Patients also undergo blood sample collection periodically during study for pharmacokinetic analysis of busulfan.

Patients undergo PET scans at baseline and on day 60.

After completion of study therapy, patients are followed at days 180 and 365 and then periodically thereafter.

Being tested
filgrastim, busulfan, etoposide, ifosfamide, melphalan
Keywords
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, childhood hepatoblastoma, recurrent childhood liver cancer, stage IV childhood liver cancer, adult primary liver cancer, previously treated childhood rhabdomyosarcoma, recurrent childhood rhabdomyosarcoma, previously untreated childhood rhabdomyosarcoma, metastatic childhood soft tissue sarcoma, recurrent childhood soft tissue sarcoma, recurrent adult soft tissue sarcoma, stage IV adult soft tissue sarcoma, recurrent Wilms tumor and other childhood kidney tumors, stage IV Wilms tumor, stage V Wilms tumor, rhabdoid tumor of the kidney, stage IV renal cell cancer, childhood mixed glioma, recurrent childhood cerebellar astrocytoma
Medical subject headings
Central Nervous System Neoplasms, Kidney Neoplasms, Liver Neoplasms, Retinoblastoma, Sarcoma, Neuroectodermal Tumors, Primitive, Peripheral, Hepatoblastoma, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • filgrastimBiological

    Also called G-CSF, Sargramostim

    Beginning 24 hours after chemotherapy end: 10 microgram/kg/day subcutaneously (SQ) or intravenously (IV) until absolute neutrophile count (ANC) > 1,000/mm^2.

    Starting that day, increase dose to 15 microgram/kg/day SQ or IV given as a single injection for 3 doses.

  • busulfanDrug

    Also called Busulfex, Myleran

    Part of pre-transplant conditioning chemotherapy: Administered as Busulfan 9.6 mg/kg IV (>4 yrs of age) or 13.2 mg/kg IV (< 4 years of age),every 6 hours on Days -8 through -6.

  • etoposideDrug

    Also called Eposin, VP-16

    Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 100 mg/m^2/day intravenous (IV) over 1 hour for 5 days.

  • ifosfamideDrug

    Also called Mitoxana, Ifex

    Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 1.8 g/m^2/day intravenous (IV) over 1 hour on for 5 days.

  • melphalanDrug

    Also called Alkeran

    Part of pre-transplant conditioning chemotherapy: Administered as 100 mg/m^2 intravenous (IV) over 30 min on Days -5 through -4.

  • thiotepaDrug

    Part of pre-transplant conditioning chemotherapy: Administered as 500 mg/m^2 intravenously (IV) over 2 hrs on Days -3 through -2.

  • stem cell transplantationProcedure or surgery

    Also called HPC infusion

    Regardless of whether the patient will be receiving peripheral cells or bone marrow, infusion will be intravenous on day 0, immediately after thawing.

  • tomotherapyRadiation

    We plan to deliver the total marrow irradiation (TMI) to the upper half of the body using Tomotherapy TMI as explained in this protocol. However the lower part of the body will be treated with Anterior/Posterior linac based radiation treatment. Tomotherapy will then be delivered at a dose rate so as to keep the total treatment time to no more than 30 minutes. We anticipate that the dose rate will be around 400 cGy

    /minute (instantaneous dose rate).

  • total marrow irradiationRadiation

    TMI will be delivered to all bony sites as part of the conditioning. Additional "spot" therapy to PET positive lesions, primary disease (if not previously irradiated to maximum tolerated dose), and lungs will be performed on Day +60. Cohorts of 3 patients will be treated at a total dose of 600 cGy, 900 cGy or 1200 cGy on Days -11 through -9.

  • MesnaDrug

    Also called Uromitexan®, Mesnex

    Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 1.8 g/m^2/day divided in every 6 hrs dosing for 5 days.

  • Whole lung radiationRadiation

    At Day 60, patients with prior lung metastasis should receive whole lung irradiation (1500cGy in 10 fractions).

Study groups in NCT00623077
Study groupRoleWhat they receive
Total Marrow Irradiation (MTI) with TomotherapyExperimentalTMI given prior to alkylator intensive conditioning regimen (Busulfan 9.6 mg/kg intravenously (IV) (>4 yrs of age) or 13.2 mg/kg IV (< 4 years of age), Melphalan 100 mg/m^2, Thiotepa 500 mg/m^2 for high risk solid tumor patients, Whole lung radiation 1500cGy in 10 fractions by Day 60, stem cell transplantation on day 0. Ifosfamide, etoposide, and mesna are given Days 0-4 followed by filgrastim for 3 doses. Cohorts of patients (n=3) will be treated with increasing doses of TMI (600, 1000, 1200 cGy) directed toward the bones.
Receives: Biological: filgrastim; Drug: busulfan; Drug: etoposide; Drug: ifosfamide; Drug: melphalan; Drug: thiotepa; Procedure: stem cell transplantation; Radiation: tomotherapy; Radiation: total marrow irradiation; Drug: Mesna; Radiation: Whole lung radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of tomotherapy up to 12 Gy

    is a state-of-the- art means of delivering highly conformal radiation to tumors of targeted volume with high therapeutic gain. Tomotherapy offers unique advantages over total body irridiation and is expected to improve clinical outcome. The MTD is defined as the highest dose studied for which the incidence of dose limiting toxicity is less than 33%.

    Measured: Day 42

Secondary outcomes (6)

  1. Percent of patients who had PET scans and "spot radiation" to PET-positive lesions after transplantation

    PET-CT scan is done prior to and after transplant. Radiation is given before and after transplant.

    Measured: Day 60 Post Transplant

  2. Change in bone mineral density

    the change in bone density and turnover in patients exposed to alkylator intensive conditioning regimen followed by tomographic total marrow irradiation (TMI).

    Measured: Baseline, 6 and 12 Months Post Transplantation

  3. Rate of Treatment Related Mortality in Non-TMI Treated Patients

    Determined in patients who were not treated with total marrow irradiation; all deaths without previous relapse or progression are usually considered as related to transplantation.

    Measured: Day 100 Post Transplant

  4. Rate of Primary Neutrophil Engraftment

    Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.

    Measured: Day 42

  5. Overall Survival

    Determined in patients not receiving total marrow irradiation. The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.

    Measured: From date of enrollment to date of death or censored at the date of last documented contact

  6. Disease-Free Survival

    In patients not receiving total marrow irradiation, the length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

    Measured: 1 Year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2008 (estimated)
  2. Study startAug 2005
  3. Primary completionJul 2012
  4. Study completionOct 2016

Why it stopped: Replaced by another study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00623077
Sponsor's protocol ID
2005LS023
Other IDs
UMN-MT2004-30, 0504M69306
Status last verified
Dec 2017
First submitted
22 Feb 2008
Last updated
5 Dec 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing filgrastim, busulfan and etoposide in people with Brain and Central Nervous System Tumors and Kidney Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Replaced by another study). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of tomotherapy up to 12 Gy (time frame: Day 42). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00623077.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2017.

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MT2004-30: Tomotherapy for Solid Tumors (NCT00623077) | AzTrials